Effect of Beta-sitosterol on Cholesterol-cholic Acid-induced Gallstone Formation in Mice

Beta-sitosterol has been shown to prevent gallstone formation in mice fed 1.2% cholesterol and 0.5% cholic acid (lithogenic diet). The incidence of gallstone formation in the mouse by the addition of 2.5% sitosterol in the lithogenic diet is about 35.5% in male and 25% in female. The condition of the liver, whether fatty or normal, did not correlate with the presence or absence of cholelithiasis. The serum and liver cholesterol levels of mice fed either sitosterol and cholesterol or sitosterol and cholic acid is lower than those of mice fed cholesterol or cholic acid alone. Elevation, of liver phospholipid concentration was noticed in mice fed sitosterol or a combination of sitosterol with cholesterol or cholic acid or both cholesterol and cholic acid.     

Anti-ulcer Activity of Cromakalim (BRL 34915), a Potassium-channel Opener,Against Experimentally Induced Gastric and Duodenal Ulcers in Rats and Guinea-pigs

The effect of cromakalim, a potassium-channel opener, was studied on pylorus ligation-induced, aspirin-induced and water-immersion plus restraint stress-induced gastric ulcers in rats and on histamine-induced duodenal ulcer in guinea-pigs. Pretreatment with cromakalim (50–500 μg kg^?1, p.o.) resulted in a significant reduction in the incidence of gastric and duodenal ulceration in each model. The anti-ulcer activity of cromakalim was comparable with that of cimetidine. Cromakalim at 100, 250 and 500 μg kg^?1 caused a reduction in the volume of the gastric content in pylorus-ligated rats, and a dose of 250 μg kg^?1 resulted in a significant reduction in total acidity (28.81 ± 11.73 mEq L^?1, P < 0.02) in the pylorus ligation model. A significant reduction in total acid output was observed at doses of 250 μg kg^?1 (84.27 ± 22.33 mEqH+, P < 0.02) and 500 μg kg^?1 (120.17 ± 24.49 mEq H+, P < 001) in pylorus-ligated rats. A significant reduction in the ulcer index in pylorus-ligated rats was observed at all cromakalim doses: 50 μg kg^?1 (0.23 ± 009, P < 0.05), 100 μg kg^?1 (0.15 ± 0009, P < 0.02), 250 μg kg^?1 (0.12 ± 0.05, P < 0.01) and 500 μg kg^?1 (0.14 ± 0.03, P < 0.02). A significant reduction in the ulcer index of aspirin-treated rats was also observed at all cromakalim dose levels: 50 μg kg^?1 (0.39 ± 0.03. P < 0.01), 100 μg kg^?1 (0.28 ± 0.06, P < 0.01), 250 μg kg^?1 (0.22 ± 0.04, P < 0.001) and 500 μg kg^?1 (0.28 ± 0.03, P < 0.01). In the water-immersion plus restraint stress-induced gastric ulcer model, cromakalim significantly reduced gastric ulceration at all the dose levels: 50 μg kg^?1 (28.2 ± 2.12, P < 0.001), 100 μg kg^?1 (20.24 ± 1.71, P < 0.01), 250 μg kg^?1 (19.95 ± 1.46, P < 0.001) and 500 μg kg^?1 (21.61 ± 3.00, P < 0.001) but there was no consistent reduction of gastric bleeding. In addition to gastric ulcers, duodenal lesions were also reduced by pretreatment with cromakalim at all dose levels: 50 μg kg^?1 (97.87 ± 20.03 mm², P < 0.02). 100 μg kg^?1 (70.72 ± 12.82 mm², P < 0.02), 250 μg kg^?1 (48.32 ± 8.42 mm², P < 0.01) and 500 μg kg^?1 (55.50 ± 12.50 mm², P < 0.01). Cromakalim at a dose of 100 μg kg^?1 also reduced total acidity (99.36 ± 9.12 mEq L^?1, P < 0.02) and total acid output (172.22 ± 45.33 mEq of H+, P < 0.05) in this model. These findings demonstrate the anti-ulcer activity of cromakalim in different experimental models and suggest its potential use in ulcer therapy.